家猪肝动脉内给予^(32)磷-玻璃微球的毒性反应研究

Acute and subacute toxic response to intrahepatic arterial administration of phosporus 32 glass microspheres in pigs

目的 评估正常家猪肝动脉内给予３２ 磷玻璃微球（３２ＰＧＭＳ） 后的急性和亚急性毒性反应。方法 １０ 只健康家猪经皮肝动脉内接受人类治疗剂量的３２ＰＧＭＳ（５ 只猪）、惰性３１ＰＧＭＳ（５ 只猪） ；２ 只猪作全程空白对照。术后按第１ 、２、４ 、８ 或１６ 周分期处以安乐死，取不同部位的肝组织进行光镜、电镜检查和超微形态计量分析。结果 给药组１、２ 周肝细胞核异常率（Ｎａｂｎ） 和线粒体变异率（ Ｍｖａｒ） 与其他各组比较差异均有显著性（ Ｐ＜ ０．０１，Ｐ＜ ０ ．００１）；给药组第８ 周与第１６ 周比较Ｎａｂｎ 无统计学意义（ Ｐ＞０ ．２０）。给药后第１、２ 周异常肝细胞多见；第４ 周异常肝细胞减少，血窦内皮破坏明显；第８ 周异常肝细胞少见，血窦内皮修复；第１６ 周肝组织形态学表现正常。结论 ３２ＰＧＭＳ肝动脉给药正常肝组织宏观吸收剂量不超过１９０Ｇｙ 只是引起临床上允许的肝内变化，肝脏组织损伤修复的时间约８ 周以上。

Objective\ To evaluate the acute and subacute toxic response to intrahepatic arterial administration of phosphorus 32 glass microspheres ( 32 P GMS) in pigs. Methods\ Through selective catheterization of hepatic artery to infuse 32 P GMS to 5 healthy domestic pigs, or inert 31 P GMS in the same procedure to other 5 healthy domestic pigs. Two pigs served as whole course blank control. One pig from each group was surrendered to euthanasis at week 1, week 2, week 4, week 8 or week 16, liver biopsies were performed in the rest pigs at the corresponding time points. Liver tissues at different sites were taken for light and electron microscopy. The ultrastructural histopathological changes were evaluated semiquantitatively. Results\ There was no different in the experimental group ( P >0.50) between the nuclear abnormality (N abn ) and mitochondrial variability (M var ) at week 1 or week 2, but revealed prominent difference ( P<0.01, P <0.001) as compared with those in other groups. In the experimental group the Nabn in tissues of week 8 and week 6 showed no significant difference ( P >0.20). The abnormal hepatocytes were easily found at week 1 or week 2. The abnormal hepatocytes at week 4 were less than those at week 1 or week 2, endothelium of the sinuses damaged prominently. The abnormal hepatocytes were scarcely seen at week 8, liver tissues repaired gradually. The histological features of liver tissue restored to normal at week 16. Conclusion Intrahepatic arterial administration of 32 P GMS at the macrocosmic absorbed dosage was less than 190 Gy, that intrahepatic change of clinically permissible extent might be induced in the liver tissue. It took more than 8 weeks for repairing the injured liver tissues and restoring its liver function.